Circulating Histone Signature of Human Lean Metabolic-associated Fatty Liver Disease (MAFLD)

Overview

Journal Clin Epigenetics

Publisher Biomed Central

Specialty Genetics

Date 2020 Aug 22

PMID 32819448

Citations 20

Authors

Diana Buzova

Andrea Maugeri

Antonio Liguori

Cecilia Napodano

Oriana Lo Re

Jude Oben

Anna Alisi

Antonio Gasbarrini

Antonio Grieco

Jan Cerveny

Luca Miele

Manlio Vinciguerra

Affiliations

Soon will be listed here.

Abstract

Background: Although metabolic associate fatty liver disease (MAFLD) is associated with obesity, it can also occur in lean patients. MAFLD is more aggressive in lean patients compared to obese patients, with a higher risk of mortality. Specific biomarkers to diagnose differentially lean or overweight MAFLD are missing. Histones and nucleosomes are released in the bloodstream upon cell death. Here, we propose a new, fast, imaging and epigenetics based approach to investigate the severity of steatosis in lean MAFLD patients.

Results: A total of 53 non-obese patients with histologically confirmed diagnosis of MAFLD were recruited. Twenty patients displayed steatosis grade 1 (0-33%), 24 patients with steatosis grade 2 (34-66%) and 9 patients with steatosis grade 3 (67-100%). The levels of circulating nucleosomes were assayed using enzyme-linked immunosorbent assay, while individual histones or histone dimers were assayed in serum samples by means of a new advanced flow cytometry ImageStream(X)-adapted method. Circulating nucleosome levels associated poorly with MAFLD in the absence of obesity. We implemented successfully a multi-channel flow methodology on ImageStream(X), to image single histone staining (H2A, H2B, H3, H4, macroH2A1.1 and macroH2A1.2). We report here a significant depletion of the levels of histone variants macroH2A1.1 and macroH2A1.2 in the serum of lean MAFLD patients, either individually or in complex with H2B.

Conclusions: In summary, we identified a new circulating histone signature able to discriminate the severity of steatosis in individuals with lean MAFLD, using a rapid and non-invasive ImageStream(X)-based imaging technology.

Citing Articles

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Extracellular Histones Profiles of Pediatric H3K27-Altered Diffuse Midline Glioma.

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MAFLD: an ideal framework for understanding disease phenotype in individuals of normal weight.

Pan Z, Khatry M, Yu M, Choudhury A, Sebastiani G, Alqahtani S Ther Adv Endocrinol Metab. 2024; 15:20420188241252543.

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Genetic and epigenetic determinants of non-alcoholic fatty liver disease (NAFLD) in lean individuals: a systematic review.

Njei B, Al-Ajlouni Y, Ugwendum D, Abdu M, Forjindam A, Mohamed M Transl Gastroenterol Hepatol. 2024; 9:11.

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